Project Summary/Abstract ? Overall The Fred Hutch Lung SPORE consists of four innovative projects, three supportive cores, and the required Developmental Research Program and Career Enhancement Program. We have leveraged the strengths of the investigators and our Center to tackle three critical barriers precluding meaningful improvements in lung cancer survival rates: facilitation of pulmonary nodule evaluation for lung cancer early detection and screening, lack of effective therapies for small cell lung cancer (SCLC), and the sub-optimal response rates of non-small cell lung cancer (NSCLC) patients to novel immune-based therapies. To overcome these barriers, we propose the following four projects: 1) Targeting the Neutrophil Lineage to Enhance Immune Checkpoint Inhibitor Efficacy in NSCLC, 2) Targeting Neoantigens for Lung Cancer Immunotherapy, 3) Identifying Determinants of Sensitivity to LSD1 Inhibition in SCLC, and 4) Risk Stratification for Pulmonary Nodules Detected by CT Imaging Using Plasma and Imaging Biomarkers. These projects will be supported by an Administrative Core, a Biostatistics and Bioinformatics Core (BBC), and a Histopathology and Biospecimen Core (HBC).